Our prospective-audit-and-feedback antimicrobial stewardship (AS) program for hematology and oncology inpatients was switched from one led by dedicated clinicians to a rotating team of infectious diseases trainees in order to provide learning opportunities and attempt a “de-escalation” of specialist input towards a more protocol-driven implementation. However, process indicators including the number of recommendations and recommendation acceptance rates fell significantly during the year, with accompanying increases in broad-spectrum antibiotic prescription. The trends were reversed only upon reverting to the original setup. Dedicated clinicians play a crucial role in AS programs involving immunocompromised patients. Structured training and adequate succession/contingency planning is critical for sustainability.

Background The optimal way for antimicrobial stewardship programs (ASPs) to interact with existing infectious disease physician (IDP) services within the same institution is unknown. In our institution, IDPs and our prospective audit and feedback ASP operate independently, with occasionally differing recommendations offered for the same inpatient. We performed a retrospective audit on inpatients that had been reviewed by both IDPs and ASP within a 7-day period, focusing on cases where different therapy-modifying recommendations had been offered. We analyzed the outcomes in inpatients where the ASP recommendations were accepted and compared these with the inpatients where the IDP recommendations were accepted instead. Outcomes assessed were 30-day mortality post-ASP review, unplanned re-admission within 30 days post-discharge from hospital, and clinical deterioration at 7 days post-ASP review. Findings There were 143 (18.9%) patients where differing recommendations had been offered, with primary physicians accepting 69.9% of ASP recommendations. No significant differences in terms of demographics, clinical characteristics, 30-day mortality, and re-admission rates were observed, although clinical deterioration rates were lower in patients where the ASP recommendation was accepted (8.0% vs. 27.9%; p = 0.002). On multivariate analysis, hematology-oncology inpatients were associated with unplanned readmission. Increasing age and hematology-oncology inpatients were associated with clinical deterioration 7 days post-recommendation, whereas acceptance of ASP recommendations was protective. No characteristic was independently associated with 30-day mortality. Conclusion In conclusion, independent reviews by both IDPs and ASPs can be compatible within large tertiary hospitals, providing primary physicians even in situations of conflicting recommendations viable alternative antimicrobial prescribing advice.

Antimicrobial resistance among uropathogens is a particularly pressing problem in the Asia-Pacific region. The objectives of this study were to determine the incidence and susceptibility of uropathogens upon hospital admission and to develop a risk-scoring model to predict the presence of ceftriaxone-resistance uropathogens (CrP). This was a retrospective observational cohort study of patients with a positive urine culture within 48 h of presentation at National University Hospital, Singapore between June 2015 and August 2015. Escherichia coli was the most common uropathogen isolated (51.7%), followed by Klebsiella pneumonia (15.1%) and Pseudomonas aeruginosa (8.2%). Overall, 372 out of 869 isolates (42.8%) were resistant to ceftriaxone. Hospitalization for ≥2 days within past 30 days, antibiotic use within the past 3 months and male gender were associated with the presence of CrP. A risk score based on these parameters successfully predicted CrP with an area under the curve of 0.68. The risk score will help clinicians to accurately predict antibiotic resistance at the individual patient level and allow physicians to safely prescribe empiric ceftriaxone in patients at low risk of CrP, thus reducing the antibiotic selection pressure that is driving carbapenem resistance in hospitals throughout Asia.

Purpose: Antimicrobial resistant infections are common in patients on haemodialysis, often needing long courses of carbapenems. This results in a longer hospital stay and risk of iatrogenic complications. However, carbapenems can be given intermittently to allow for earlier discharge. We aim to describe the clinical outcomes of intermittent versus daily meropenem in stable, intermittently haemodialysed patients. Methods: In total, 103 records were examined retrospectively. Data collected include demographics, clinical interventions and outcomes such as hospital length of stay (LOS), 30-day readmission rates and adverse events. Findings: Mean age 61.6 ± 14.2 years, 57.3% male. Most common bacteria cultured were Klebsiella pneumoniae (16.5%). The most common indication was pneumonia (27.2%). Mean duration of therapy on meropenem was 12.4 ± 14.4 days; eight patients needed more than 30 days of meropenem. In total, 55.3% did not have intervention for source control; 86.4% received daily dosing of meropenem; 7.8% patients received intermittent dosing of meropenem only, and 5.8 patients received both types of dosing regimens. LOS of the index admission was shorter for the intermittent arm (15.5 ± 7.6 days versus daily: 30.2 ± 24.5 days), though 30-day readmission was higher (50% versus daily: 38.2%). Implications: We recommend further rigorous randomised controlled trials to investigate the clinical utility of intermittent meropenem dosing in patients on stable haemodialysis.

Monoclonal antibodies targeting immune checkpoints have demonstrated clinical success in a range of tumor types; however sustained responses are achieved in a fraction of patients due to primary or secondary resistance to treatment. Recent evidence has implicated the pleiotropic immunosuppressive modulator Galactoside-binding lectin Galectin 9 (Gal-9) as a key factor in the tumor microenvironment that renders tumors resistant to current chemo and immunotherapies. High Gal-9 expression has been reported in different types of cancer, including hematological malignancies such as AML and ALL, and multiple solid tumors. Previously, we have described the characterization of an anti-human Gal-9 antibody, HFB9-2, with sub-nanomolar affinity for human, murine and cynomolgous Gal-9. HFB9-2 blocks the interaction of Gal-9 with its receptors TIM3 and CD44, leading to inhibition of Gal-9 mediated Th1 cell apoptosis and regulatory T cell expansion. HFB9-2 demonstrated significant anti-tumor efficacy and increased survival in a WEHI-164 syngeneic model as a single agent and in combination with anti-PD1 antibody. HFB9-2 is well tolerated in cynomolgous monkeys after administered by intravenous infusion as a single dose of 10, 50, 200 mg/kg, with no adverse effects and a NOAEL of 200 mg/kg. HFB9-2 developability profile assessment does not anticipate any stability and manufacturing issues. We hypothesize that targeting Gal-9 represents a valuable strategy to reduce immunosuppression and improve clinical response in selected cancer patients, in particular AML. Gal-9 has been reported to play a dual role in AML as both a self-renewal factor for leukemic stem cells and a suppressor of anti-cancer immunity. Analysis of AML patient serum samples demonstrated that Gal-9 expression was significantly higher than in healthy controls and that dropped at complete remission. Higher levels of Gal-9 were found in French-America-British (FAB) type M4 and M5 AML samples, and the lowest levels were observed in M3. To better understand the role for Gal-9 in the development of AML, we implanted primary human AML cells from different donors in M-NSG mice (NOD-Prkdc^scid Il2rg^em1). We demonstrate that the engraftment of primary human AML cells in these mice resulted in high levels of human Gal-9 in their serum that were detectable 2 weeks after intravenous implantation. The serum levels of Gal-9 increased over time following the increase of hCD45+ AML cells. Further analysis to evaluate the effect of Gal-9 neutralization in AML progression after primary and secondary engraftment with HFB9-2 are currently ongoing. The data presented here provide evidence that neutralization of Gal-9 with HFB9-2 blocks key immunosuppressive mechanisms known to favor cancer progression and to limit the efficacy of current immunotherapies, and together with the data obtained in AML patient samples position Gal-9 neutralization as a promising anticancer approach. Citation Format: Germain Margall, Muriel David, Julie Prigent, Dean Lee, Wenhua Xu, Joyce Pi, Xing Cai, He Zhou, Andreas Raue, Nicola Beltraminelli, Mingjie Chen, Jia Wu, Mingfang Feng, Angelo Paci, Julia Delahousse, Véronique Saada, Stéphane de Botton, Pierre Busson, Stephanie Beq, Francisco Adrian, Liang Schweizer, Yun-Yueh Lu. HFB9-2, a novel Galectin 9 neutralizing antibody for the treatment of AML and other cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1884.